rs150097149
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The ENST00000270722.10(PRDM16):c.429C>T(p.Cys143=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000138 in 1,613,870 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00079 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 0 hom. )
Consequence
PRDM16
ENST00000270722.10 synonymous
ENST00000270722.10 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.61
Genes affected
PRDM16 (HGNC:14000): (PR/SET domain 16) The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene is a zinc finger transcription factor and contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant 1-3244128-C-T is Benign according to our data. Variant chr1-3244128-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 227040.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=1.61 with no splicing effect.
BS2
High AC in GnomAd4 at 121 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PRDM16 | NM_022114.4 | c.429C>T | p.Cys143= | synonymous_variant | 3/17 | ENST00000270722.10 | NP_071397.3 | |
PRDM16 | NM_199454.3 | c.429C>T | p.Cys143= | synonymous_variant | 3/17 | NP_955533.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PRDM16 | ENST00000270722.10 | c.429C>T | p.Cys143= | synonymous_variant | 3/17 | 1 | NM_022114.4 | ENSP00000270722 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000795 AC: 121AN: 152222Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000196 AC: 49AN: 249382Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135340
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GnomAD4 exome AF: 0.0000691 AC: 101AN: 1461530Hom.: 0 Cov.: 31 AF XY: 0.0000578 AC XY: 42AN XY: 727074
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GnomAD4 genome AF: 0.000794 AC: 121AN: 152340Hom.: 1 Cov.: 32 AF XY: 0.000698 AC XY: 52AN XY: 74498
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 24, 2014 | Cys143Cys in exon 3 of PRDM16: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 0.3% (13/4172) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs150097149). - |
PRDM16-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 04, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2020 | - - |
Left ventricular noncompaction 8 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at